Emerging Treatments for Psoriasis
Recently approved therapies, drugs in development, and expanded labels for existing psoriasis drugs continue to offer clinicians and patients an expanding range of options for treatments.
The psoriasis treatment landscape continues to expand. In 2017, 3 new drugs gained FDA approval for the treatment of psoriatic arthritis (PsA) and in March 2018 a new monoclonal antibody, tildrakizumab (Ilumya) was FDA approved for plaque psoriasis. Furthermore, 2018 has already seen the expansion of indications for established therapies, such as ixekizumab (Taltz) with the possibility of new medicines gaining approval before the end of the year.
New Therapy Approvals
For PsA, abatacept (Orencia), tofacitinib (Xeljanz), intravenous (IV) golimumab (Simponi Aria), and ixekizumab were all FDA approved in 2017. Importantly, each of these medications represents a unique mechanism of action. Abatacept is a fusion protein administered subcutaneously for the treatment of PsA, which binds to antigen presenting cells and thereby disrupts T-cell activation. It gained FDA approval based on a 20% improvement in the American College of Rheumatology (ACR20) metric in 39.4% of abatacept-treated patients vs 22.3% of placebo controls in a 24-week phase 3 study. Unfortunately, “the psoriatic skin response was more modest compared with the musculoskeletal response.”1 Dermatologists should be aware of this new indication, however, as the concomitant use of abatacept and tumor necrosis factor (TNF) inhibitors has been shown to be associated with increased risks of infection and is contraindicated.
Tofacitinib, an oral Janus kinase 1 and 3 (JAK1 & JAK3) inhibitor that modulates inflammatory cytokine production by disrupting the JAK-STAT signaling pathway, was approved for the treatment of PsA in August 2017 based on results from 2 phase 3 trials—OPAL Beyond and OPAL Broaden. In OPAL Beyond, 50% of patients receiving tofacitinib 5 mg orally twice daily reached ACR20 vs 24% in the placebo group at 3 months.2 In OPAL Broaden, 50% of patients receiving tofacitinib achieved ACR20 vs 33% in the placebo group at 3 months.3 A Psoriasis Area and Severity Index (PASI 75) response was recorded in 21.3% of patients receiving tofacitinib 5 mg twice daily in OPAL Beyond and 42.7% in OPAL Broaden.4,5 Radiographic evidence of disease progression was also examined, however, rates of nonprogression were similar across all groups and thus “treatment effect on inhibition of radiographic progression in PsA could not be established.”6 To improve patient convenience and compliance, tofacitinib is also available as an 11-mg extended release tablet (Xeljanz XR) to be taken once daily.
In October 2017, golimumab became the only fully human, anti-TNF antibody approved for IV infusion. Previously approved for rheumatoid arthritis the label was expanded to include PsA based on phase 3 testing that showed 75.1% of patients treated with 2 mg/kg of IV golimumab achieving an ACR20 vs 21.8% in the placebo group at week 14. Inhibition of structural joint damage as compared to those in the placebo arms was noted at week 24.7
Expansions of Treatment
The ixekizumab label also recently expanded with the FDA approval for the treatment of PsA, and a label update to include genital psoriasis. Approval for the treatment of PsA was granted in December 2017 based on the results of two 24-week phase 3 trials, SPIRIT-P18 and SPIRIT P-2.9 In SPIRIT-P1, 58% of patients treated with ixekizumab 80 mg subcutaneous (SC) every 4 weeks achieved an ACR20 response compared with 30% in the placebo group, while 53% similarly treated with ixekizumab in SPIRIT-P2 achieved an ACR20 compared with 34% in the placebo arm. In addition, as a result of data gathered in SPIRIT-P1, ixekizumab became the first anti-IL-17A antibody to include efficacy data detailing the inhibition of structural joint damage progression in the package insert.10
In May 2018, ixekizumab also became the first biologic to receive a label update from the FDA for use in genital psoriasis. Approval was based on a phase 3 trial in which patients who had “failed to respond to or were intolerant of at least one topical therapy” were treated with 160 mg SC of ixekizumab followed by 80 mg every 2 weeks for 12 weeks. The trial’s primary endpoint was the proportion of individuals achieving a static Physician’s Global Assessment (PGA) rating of 0 or 1, indicating clear or minimal genital psoriasis. A total of 73% of treated patients reached this primary endpoint.11
Ixekizumab and secukinumab (Cosentyx) exclusively block and bind to the cytokine IL-17A. In contrast, brodalumab (Siliq), binds and blocks the IL-17RA receptor. Brodalumab blocks the activity of 5 IL-17 subtypes: IL-17A, IL-17C, IL-17E (IL-25), and IL-17F, but recent research suggests future antibodies may target both IL-17A and IL-17F simultaneously. Results from a phase 2b dose-ranging study for bimekizumab, a humanized IgG1 monoclonal antibody which selectively binds and inhibits IL-17A and IL-17F, were recently published. Increasing efficacy was noted with increasing dosage, and 79.1% of patients achieved a PASI 90 and 60% achieved a PASI 100 vs 0% in the placebo at 12 weeks.12 A similarly designed trial was conducted for PsA; however, results have not yet been published for peer review. 13
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